A. Lemmers is a research fellow and T. Gustot is a post-doctoral researcher of the FNRS.
Article first published online: 9 OCT 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 49, Issue 2, pages 646–657, February 2009
How to Cite
Lemmers, A., Moreno, C., Gustot, T., Maréchal, R., Degré, D., Demetter, P., de Nadai, P., Geerts, A., Quertinmont, E., Vercruysse, V., Le Moine, O. and Devière, J. (2009), The interleukin-17 pathway is involved in human alcoholic liver disease. Hepatology, 49: 646–657. doi: 10.1002/hep.22680
This study has been selected for oral presentation during the AASLD Liver meeting 2008.
Potential conflict of interest: Nothing to report.
- Issue published online: 28 JAN 2009
- Article first published online: 9 OCT 2008
- Accepted manuscript online: 9 OCT 2008 12:00AM EST
- Manuscript Accepted: 18 SEP 2008
- Manuscript Received: 18 APR 2008
- Belgian “National Fund for Scientific Research” (FNRS)
- Erasme Foundation
Immune dysregulations in alcoholic liver diseases are still unclear, especially regarding alcoholic hepatitis inflammatory burst. Interleukin-17 (IL-17) is known to enhance neutrophil recruitment. We studied the IL-17 pathway in alcoholic cirrhosis and alcoholic hepatitis. Patients with alcoholic liver disease were compared with patients with chronic hepatitis C virus (HCV) infection or autoimmune liver disease and with healthy controls. IL-17 plasma levels and peripheral blood mononuclear cell secretion were assessed by enzyme-linked immunosorbent assay (ELISA) and T cell phenotype by flow cytometry. IL-17 staining and co-staining with CD3 and myeloperoxidase were performed on liver biopsy specimens. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by chemotaxis assays. IL-17 plasma levels were dramatically increased in alcoholic liver disease patients. Peripheral blood mononuclear cells of patients with alcoholic liver disease produced higher amounts of IL-17, and their CD4+ T lymphocytes disclosed an IL-17–secreting phenotype. In the liver, IL-17–secreting cells contributed to inflammatory infiltrates in alcoholic cirrhosis, and alcoholic hepatitis foci disclosed many IL-17+ cells, including T lymphocytes and neutrophils. In alcoholic liver disease, liver IL-17+ cells infiltrates correlated to model for end-stage liver disease score, and in alcoholic hepatitis to modified discriminant function. IL-17 receptor was expressed in alcoholic liver disease by hepatic stellate cells, and these cells recruited neutrophils after IL-17 stimulation in a dose-dependent manner through IL-8 and growth related oncogen α (GRO-α) secretion in vitro. Conclusion: Human alcoholic liver disease is characterized by the activation of the IL-17 pathway. In alcoholic hepatitis, liver infiltration with IL-17–secreting cell infiltrates is a key feature that might contribute to liver neutrophil recruitment. (Clinical trials number NCT00610597). (HEPATOLOGY 2009;49:646–657.)